Honey bee (Apis mellifera) exposomes and dysregulated metabolic pathways associated with Nosema ceranae infection

Honey bee (Apis mellifera) health has been severely impacted by multiple environmental stressors including parasitic infection, pesticide exposure, and poor nutrition. The decline in bee health is therefore a complex multifactorial problem which requires a holistic investigative approach. Within the exposome paradigm, the combined exposure to the environment, drugs, food, and individuals' internal biochemistry affects health in positive and negative ways. In the context of the exposome, honey bee hive infection with parasites such as Nosema ceranae is also a form of environmental exposure. In this study, we hypothesized that exposure to xenobiotic pesticides and other environmental chemicals increases susceptibility to N. ceranae infection upon incidental exposure to the parasite. We further queried whether these exposures could be linked to changes in conserved metabolic biological pathways. From 30 hives sampled across 10 sites, a total of 2,352 chemical features were found via gas chromatography-time of flight mass spectrometry (GC-TOF) in extracts of honey bees collected from each hive. Of these, 20 pesticides were identified and annotated, and found to be significantly associated with N. ceranae infection. We further determined that infected hives were linked to a greater number of xenobiotic exposures, and the relative concentration of the exposures were not linked to the presence of a N. ceranae infection. In the exposome profiles of the bees, we also found chemicals inherent to known biological metabolic pathways of Apis mellifera and identified 9 dysregulated pathways. These findings have led us to posit that for hives exposed to similar chemicals, those that incur multiple, simultaneous xenobiotic stressors have a greater incidence of infection with N. ceranae. Mechanistically, our results suggests the overwhelming nature of these exposures negatively affects the biological functioning of the bee, and could explain how the decline in bee populations is associated with pesticide exposures

Increased alarm pheromone component is associated with <italic toggle="yes">Nosema ceranae</italic> infected honeybee colonies

Use of chemicals, such as alarm pheromones, for rapid communication with conspecifics is widespread throughout evolutionary history. Such chemicals are particularly important for social insects, such as the honeybee (Apis mellifera), because they are used for collective decision-making, coordinating activities and self-organization of the group. What is less understood is how these pheromones change due to an infection and what the implications might be for social communication. We used semiquantitative polymerase chain reaction (sqPCR) to screen for a common microsporidian gut parasite, Nosema ceranae, for 30 hives, across 10 different locations. We then used high-resolution accurate mass gas chromatography–quadrupole time of flight mass spectrometry to generate an exposome profile for each hive. Of the 2352 chemical features identified, chemicals associated with infection were filtered for cosanes or cosenes. A significant association was found between N. ceranae and the presence of (Z)-11-eicosen-1-ol, a known alarm pheromone component. The increase in (Z)-11-eicosen-1-ol could be the recognition mechanism for healthy individuals to care for, kill, or quarantine infected nestmates. Nosema ceranae has contributed to the global decline in bee health. Therefore, altered alarm pheromones might play a role in disrupting social harmony and have potential impacts on colony health

Statistical nodels to explore the exposome: from OMICs profiling to ‘mechanome’ characterization

Over the past decade, high-resolution molecular profiles using OMICS technologies have accumulated and have given rise to an unprecedented source of information to explore the effective biological effects of external stressors and to detect drivers of subsequent disease risk. Although the volume, dimensionality, and complexity of OMICs data are constantly increasing, several methods enabling their analysis are now available. The exploration of these data relies on statistical approaches including univariate models coupled with multiple testing correction, dimensionality reduction techniques, and variable selection approaches. While these methods are established, their application in an exposome context is raising specific methodological challenges. In addition, the isolated exploration of an OMIC profile offers the possibility to capture stressor-induced biological/biochemical alterations, potentially impacting individual risk profiles, but this may only yield a fractional picture of the complex molecular events involved, therefore limiting our understanding of the effective mechanisms mediating the effect of the exposome. Despite efficient developments over systems biological approaches, such integrations remain at best data-specific, usually disease-specific, and more systematically restricted to the exploration of (few) predefined hypotheses. The challenging task of exploring the ‘mechanome’ as defined by the ensemble of stressor-induced molecular mechanisms occurring throughout the life course and determining the individual’s risk of developing adverse conditions can be decomposed in three interdependent streams focusing on (1) OMICs profiling, (2) OMICs data integration, and (3) the exploration of molecular mechanisms involved in the exposure effect mediation towards (chronic) disease development

Correction: Honey bee (Apis mellifera) exposomes and dysregulated metabolic pathways associated with Nosema ceranae infection.

[This corrects the article DOI: 10.1371/journal.pone.0213249.]

Silicone wristbands as passive samplers in honey bee hives

The recent decline of European honey bees (Apis mellifera) has prompted a surge in research into their chemical environment, including chemicals produced by bees, as well as chemicals produced by plants and derived from human activity that bees also interact with. This study sought to develop a novel approach to passively sampling honey bee hives using silicone wristbands. Wristbands placed in hives for 24 h captured various compounds, including long-chain hydrocarbons, fatty acids, fatty alcohols, sugars, and sterols with wide ranging octanol-water partition coefficients (Kow) that varied by up to 19 orders of magnitude. Most of the compounds identified from the wristbands are known to be produced by bees or plants. This study indicates that silicone wristbands provide a simple, affordable, and passive method for sampling the chemical environment of honey bees

Exposure to Persistent Organic Pollutants (POPs) and Their Relationship to Hepatic Fat and Insulin Insensitivity among Asian Indian Immigrants in the United States

Persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and other organochlorine compounds, are abundant in the environment and in foodstuffs from the Indian subcontinent. These environmental contaminants have been associated with a higher risk of diabetes in numerous studies. Asian Indians are well known to have a high risk of diabetes compared with other populations, and this risk is also found in migrant populations of Asian Indians in the United States, Europe, and elsewhere. We hypothesized that high plasma concentrations of POPs in Asian Indian migrants are linked to a variety of diabetes-related pathologies and explored the mechanism for the induction of these effects. We measured 30 environmental pollutants in plasma samples obtained from 147 participants in the Metabolic syndrome and Atherosclerosis in South Asians Living in America pilot study using a gas chromatography-tandem mass spectrometry analytical method that uses less than 0.5 mL of plasma. We found that plasma levels of o,p'-DDT and p,p'-DDT were independently associated with both body mass index (BMI) and waist circumference. Doubling the levels of the sums of these DDTs was associated with insulin insensitivity (-0.38 Matsuda index, p = 0.001), increased adiposity (1.26 kg/m2 BMI and 3.58 cm waist circumference increase, p &lt; 0.0001), circulating insulin (12.9 mIU/L, p = 0.002), hepatic fat (-0.051 HU, p = 0.001), as well as increased odds of obesity (OR = 2.17, p &lt; 0.001, BMI-based; OR = 2.37, p = 0.001, waist-based), prediabetes (OR = 1.55, p = 0.02), diabetes (OR = 1.72, p = 0.01), and fatty liver (OR = 1.66, p = 0.01) in multivariable models accounting for confounding by age, sex, years in the US, education, and fish protein. Furthermore, levels of DDTs were associated with increased hepatic fat and circulating insulin, independent of obesity and confounders. These findings suggest that exposure to DDTs may contribute to the risk of metabolic disease among Asian Indians by affecting hepatic fat levels independent of obesity

Environmental exposures associated with honey bee health

Bee health is declining on a global scale, yet the exact causes and their interactions responsible for the decline remain unknown. To more objectively study bee health, recently biomarkers have been proposed as an essential tool, because they can be rapidly quantified and standardized, serving as a comparable measure across bee species and varying environments. Here, we used a systems biology approach to draw associations between endogenous and exogenous chemical profiles, with pesticide exposure, or the abundance of the 21 most common honey bee diseases. From the analysis we identified chemical biomarkers for both pesticide exposure and bee diseases along with the mechanistic biological pathways that may influence disease onset and progression. We found a total of 2352 chemical features, from 30 different hives, sampled from seven different locations. Of these, a total of 1088 significant associations were found that could serve as chemical biomarker profiles for predicting both pesticide exposure and the presence of diseases in a bee colony. In almost all cases we found novel external environmental exposures within the top seven associations with bee diseases and pesticide exposures, with the majority having previously unknown connections to bee health. We highlight the exposure-outcome paradigm and its ability to identify previously uncategorized interactions from different environmental exposures associated with bee diseases, pesticides, mechanisms, and potential synergistic interactions of these that are responsible for honey bee health decline

Elevated Levels of Organochlorine Pesticides in South Asian Immigrants are Associated with an Increased Risk of Diabetes

ObjectiveRates of diabetes mellitus are higher in South Asians than in other populations and persist after migration. One unexplored cause may be higher exposure to persistent organic pollutants associated with diabetes in other populations. We compared organochlorine (OC) pesticide concentrations in South Asian immigrants and European whites to determine whether the disease was positively associated with OC pesticides in South Asians.Research design and methodsSouth Asians of Tamil or Telugu descent (n = 120) and European whites (n = 72) were recruited into the London Life Sciences Population Study cohort. Blood samples as well as biometric, clinical, and survey data were collected. Plasma levels of p,p'-dichlorodiphenyldichloroethylene (DDE), p,p'- dichlorodiphenyltrichloroethane, β-hexachlorohexane (HCH), and polychlorinated biphenyl-118 were analyzed by gas chromatography-mass spectrometry. South Asian cases and controls were categorized by binary exposure (above vs below the 50th percentile) to perform logistic regression.ResultsTamils had approximately threefold to ninefold higher levels of OC pesticides, and Telugus had ninefold to 30-fold higher levels compared with European whites. The odds of exposure to p,p'-DDE above the 50th percentile was significantly greater in South Asian diabetes cases than in controls (OR: 7.00; 95% CI: 2.22, 22.06). The odds of exposure to β-HCH above the 50th percentile was significantly greater in the Tamil cases than in controls (OR: 9.35; 95% CI: 2.43, 35.97).ConclusionsSouth Asian immigrants have a higher body burden of OC pesticides than European whites. Diabetes mellitus is associated with higher p,p'-DDE and β-HCH concentrations in this population. Additional longitudinal studies of South Asian populations should be performed

Elevated levels of organochlorine pesticides in South Asian immigrants are associated with an increased risk of diabetes

Objective: Rates of diabetes mellitus are higher in South Asians than in other populations and persist after migration. One unexplored cause may be higher exposure to persistent organic pollutants associated with diabetes in other populations. We compared organochlorine (OC) pesticide concentrations in South Asian immigrants and European whites to determine whether the disease was positively associated with OC pesticides in South Asians. Research Design and Methods: South Asians of Tamil or Telugu descent (n = 120) and European whites (n = 72) were recruited into the London Life Sciences Population Study cohort. Blood samples as well as biometric, clinical, and survey data were collected. Plasma levels of p,p′-dichlorodiphenyldichloroethylene (DDE), p,p′- dichlorodiphenyltrichloroethane, β-hexachlorohexane (HCH), and polychlorinated biphenyl-118 were analyzed by gas chromatography-mass spectrometry. South Asian cases and controls were categorized by binary exposure (above vs below the 50th percentile) to perform logistic regression. Results: Tamils had approximately threefold to ninefold higher levels of OC pesticides, and Telugus had ninefold to 30-fold higher levels compared with European whites. The odds of exposure to p,p′-DDE above the 50th percentile was significantly greater in South Asian diabetes cases than in controls (OR: 7.00; 95% CI: 2.22, 22.06). The odds of exposure to β-HCH above the 50th percentile was significantly greater in the Tamil cases than in controls (OR: 9.35; 95% CI: 2.43, 35.97). Conclusions: South Asian immigrants have a higher body burden of OC pesticides than European whites. Diabetes mellitus is associated with higher p,p′-DDE and β-HCH concentrations in this population. Additional longitudinal studies of South Asian populations should be performed.NMRC (Natl Medical Research Council, S’pore)MOH (Min. of Health, S’pore)Published versio